A novel role of CD30L/CD30 signaling by T-T cell interaction in Th1 response against mycobacterial infection.
A CD30 ligand (CD30L, CD153) is a type II membrane-associated glycoprotein belonging to the TNF family. To illustrate the potential role of CD30L in CD4(+) Th1 cell responses, we investigated the fate of Ag-specific CD4(+) T cells in CD30L-deficient (CD30L(-/-)) mice after Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. The number of bacteria was significantly higher in organs of CD30L(-/-) mice than in wild-type (WT) mice 4 wk postinfection. The numbers of purified protein derivative- or Ag85B-specific-IFN-gamma-producing-CD4(+) T cells in spleen, lung, or peritoneal exudate cells were significantly fewer in CD30L(-/-) mice than in WT mice. During the infection, CD30L was expressed mainly by CD44(+)CD3(+)CD4(+) T cells but not by CD3(+)CD8(+) T cells, B cells, dendritic cells, or macrophages. Costimulation with agonistic anti-CD30 mAb or coculturing with CD30L-transfected P815 cells restored IFN-gamma production by CD4(+) T cells from BCG-infected CD30L(-/-) mice. Coculturing with CD30L(+/+)CD4(+) T cells from BCG-infected WT mice also restored the number of IFN-gamma(+)CD30L(-/-)CD4(+) T cells. When transferred into the CD30L(+/+) mice, Ag-specific donor CD30L(-/-) CD4(+) T cells capable of producing IFN-gamma were restored to the compared level seen in CD30L(+/+) CD4(+) T cells on day 10 after BCG infection. When naive CD30L(+/+) T cells were transferred into CD30L(-/-) mice, IFN-gamma-producing-CD4(+) Th1 cells of donor origin were normally generated following BCG infection, and IFN-gamma-producing-CD30L(-/-)CD4(+) Th1 cells of host origin were partly restored. These results suggest that CD30L/CD30 signaling executed by CD30(+) T-CD30L(+) T cell interaction partly play a critical role in augmentation of Th1 response capable of producing IFN-gamma against BCG infection.
Tang
Ce
C
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yamada
Hisakata
H
Shibata
Kensuke
K
Muta
Hiromi
H
Wajjwalku
Worawidh
W
Podack
Eckhard R
ER
Yoshikai
Yasunobu
Y
D000818:Animals; D053285:CD30 Ligand / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
D053285:CD30 Ligand; D017730:Ki-1 Antigen; C505775:Tnfsf8 protein, mouse; D007371:Interferon-gamma